The objective is to investigate the mechanisms controlling the activation and desensitization of the synaptic membrane of sympathetic postganglionic fibers. Electrophysiological measurements will be used to follow the change in membrane conductance produced by sustained application of depolarizing quaternary salts. The initial decrease in effective transmembrane resistance will be used to estimate the extent of cholinergic receptor activation and the time course of resistance recovery during sustained exposure will be taken as an index of the onset and rate of synaptic desensitization. Of particular concern will be the effect of calcium and local anesthetics on the time course of the conductance produced synaptic activation and desensitization. In addition, the possible role of cyclic AMP in the desensitization process will be determined. It is expected that the results of the study will increase our general knowledge of the physiology and pharmacology of the cholinergic membrane at sympathetic postganglionic fibers and add insight into the role of calcium in the control of ionic flux through synaptic membranes. In the proposed project the following will be investigated: a. The influence of alteration in the extracellular concentration of calcium and other ions on the time course of desensitization. b. The influence of alteration in the intracellular calcium ion concentration on the extent of synaptic activation and rate of desensitization. c. The influence of local anesthetics on receptor activation and desensitization. d. The influence of alteration in cyclic AMP levels on the rate of desensitization.